Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery (MAPSS)

This study has been terminated.
(The study was stopped due to poor enrollment.)
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01765270
First received: January 4, 2013
Last updated: May 7, 2015
Last verified: April 2015
  Purpose
Individuals with type 2 diabetes mellitus (T2DM) are at increased risk for cardiovascular events (for example, heart attack) and the risk is related to one's overall control of blood glucose levels. In this study the investigators will measure the effects of saxagliptin, compared to placebo, before, during, and after coronary artery bypass graft (CABG) surgery. The investigators will use samples of the patients' blood and tissue to measure and evaluate indicators of the body's response to the treatment. This study is being done to evaluate the effect of saxagliptin on biomarkers of the heart to help us understand whether reducing or controlling a person's blood glucose levels during and after CABG surgery will produce better clinical outcomes (for example, better heart health).

Condition Intervention Phase
Type 2 Diabetes Mellitus
Cardiovascular Disease
Drug: Saxagliptin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Troponin I (TnI) Area Under the Curve (AUC) [ Time Frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • High Sensitive Troponin-I (hsTnT) Area Under the Curve [ Time Frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) ] [ Designated as safety issue: No ]
  • Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve [ Time Frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) ] [ Designated as safety issue: No ]
  • Number of Major Adverse Cardiac Events (MACE) [ Time Frame: Baseline to end of study (Approximately 35-37 days) ] [ Designated as safety issue: No ]
    Death, myocardial infarction (MI), or New congestive heart failure (CHF)

  • Duration of Inotropic Support [ Time Frame: CABG surg until hosp discharge (Approximately 5 days) ] [ Designated as safety issue: No ]
  • Number of Participants Who Had an Episode of Hypoglycemia [ Time Frame: baseline to end of study (Approximately 35-37 days) ] [ Designated as safety issue: No ]
  • Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support [ Time Frame: CABG to hospital discharge (Approximately 5 days) ] [ Designated as safety issue: No ]
  • Need for Antiarrhythmic Therapy [ Time Frame: CABG surg to hospital discharge Approximately 5 days ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: March 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Saxagliptin
Treatments to be administered are saxagliptin 5 mg (once daily) to begin at randomization 5 to 7 days before CABG surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery.
Drug: Saxagliptin
one 5-mg saxagliptin tablet daily
Other Name: Onglyza
Placebo Comparator: Placebo
Treatments to be administered are placebo 5 mg (once daily) to begin at randomization 5 to 7 days before CABG surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery.
Drug: Placebo
5mg placebo tablet daily

Detailed Description:
This study is a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of saxagliptin on cardiac biomarkers of myocardial necrosis, cardiac function, inflammation, and apoptosis in subjects with Type 2 diabetes mellitus (T2DM) undergoing CABG surgery (on pump, via a median sternotomy approach) as an integrated measure of the potential mechanistic effects of saxagliptin on prevention of cardiovascular (CV) outcomes. Approximately 74 subjects will be randomized and complete the study.
  Eligibility

Ages Eligible for Study:   45 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Known diagnosis of type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin (HbA1c) between 6.5% and 10%, inclusive.

    • Stable doses of oral antihyperglycemic agents for at least 2 months
    • Stable dose of chronic insulin therapy for at least 2 months
    • HbA1c documented within 3 months before study enrollment
  • Planned first elective coronary artery bypass graft (CABG) surgery

Exclusion Criteria:

  • Elevated Creatine Kinase-Myocardial Bands (CK-MB) or troponin level above the 99th percentile at screening
  • Receiving incretin therapy or having received incretin therapy within the previous 2 months
  • Type 1 DM or a history of ketoacidosis
  • Women who are pregnant or breastfeeding
  • Known end-stage Kidney disease
  • Known sensitivity or intolerance to saxagliptin or dipeptidyl peptidase-4 (DPP-4) inhibitor
  • Clinically apparent liver disease
  • History of pancreatitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765270

Locations
United States, Alabama
Cardiology, PC
Birmingham, Alabama, United States, 35211
Cardio-Thoracic Surgeons PC
Birmingham, Alabama, United States, 35243
Heart Center Research, LLC
Huntsville, Alabama, United States, 35801
United States, Arkansas
Sparks Regional Medical Center
Fort Smith, Arkansas, United States, 72901
Arkansas Cardiology, PA
Little Rock, Arkansas, United States, 72205
United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
United States, North Carolina
Duke University Medical Center (DUMC)
Durham, North Carolina, United States, 27710
United States, Virginia
Chippenham Medical Center
Richmond, Virginia, United States, 23225
United States, West Virginia
Charleston Area Medical Center (CAMC)
Charleston, West Virginia, United States, 25304
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: L. Kristin Newby, M.D., MHS Duke University
  More Information

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01765270     History of Changes
Other Study ID Numbers: Pro00041744 
Study First Received: January 4, 2013
Results First Received: April 23, 2015
Last Updated: May 7, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Diabetes
Diabetes Mellitus
Type 2 Diabetes
Cardiovascular Disease
Coronary Artery Bypass Surgery

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on July 21, 2016